Recrystallization of Commercial Carbamazepine Samples—A Strategy to Control Dissolution Variability

Felicia Flicker,Veronika A Eberle,Gabriele Betz

doi:10.3390/pharmaceutics4010058

Felicia Flicker, Veronika A Eberle + Show 1 more

Open Access

https://doi.org/10.3390/pharmaceutics4010058

Copy DOI

Journal: Pharmaceutics	Publication Date: Jan 13, 2012
Citations: 37	License type: CC BY 4.0

Affiliation: University of Basel

Abstract

Physical properties of commercial carbamazepine (CBZ) samples can significantly influence drug release and thereby jeopardize bioequivalence of the final dosage form. The aim of this study was to reduce variability in commercial CBZ samples by recrystallization. CBZ samples of four different suppliers were recrystallized in ethanol solution containing 1% polyvinylpyrrolidone (PVP). CBZ samples were analyzed by disk intrinsic dissolution rate (DIDR), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Recrystallized CBZ samples showed strongly reduced variability in DIDR compared to the untreated CBZ samples. Moreover, transformation process to CBZ dihydrate was inhibited; no dihydrate crystals were visible on compact surfaces after 8 h intrinsic dissolution measurement. Recrystallized CBZ samples showed no change in polymorphic form, however, particle size and shape was inhomogenous. In binary mixtures with microcrystalline cellulose, recrystallized CBZ samples again showed difference in drug release. This difference was associated with the inhomogenous particle size in the recrystallized CBZ samples. The results show that a controlled grinding step is required after recrystallization. We suggest the recrystallization in presence of 1% PVP followed by a controlled grinding step as a strategy to reduce dissolution variability in commercial CBZ samples.

Highlights

Pharmaceutical companies are facing a fast growing market of drug suppliers where raw materials can be obtained from suppliers in India and China at lower price
We suggest the recrystallization in presence of 1% PVP followed by a controlled grinding step as a strategy to reduce dissolution variability in commercial CBZ samples
Compacts of recrystallized CBZ samples did not show any improvement in compaction as expected by the results reported by Nokhodchi et al [16]

Summary

Introduction

Pharmaceutical companies are facing a fast growing market of drug suppliers where raw materials can be obtained from suppliers in India and China at lower price. CBZ is one example where sample variability among different suppliers effects the dissolution behavior of the tablet formulation. Šehić et al [1] reported different transformation to dihydrate within commercial CBZ samples, the same polymorphic form was specified. This difference shows in tablet formulation using Ludipress® as tablet filler. Tablet hardness, friability, and drug release varied with the CBZ sample. For CBZ, the variability in drug release is closely linked to clinical failures as the bioavailability of CBZ is dissolution controlled and the pharmacological action is within a narrow therapeutic range [3]. There have been numerous reports showing irregular dissolution [4,5,6], bioinequivalence [7,8,9], and clinical failures of CBZ [10]

Objectives

Methods

Results

Conclusion